Page 376 - Textbook of Pathology, 6th Edition

360 ESSENTIAL THROMBOCYTHAEMIA CHRONIC IDIOPATHIC MYELOFIBROSIS

Definition and Pathophysiology Definition and Pathophysiology
Essential thrombocythaemia (ET), also termed essential Chronic idiopathic myelofibrosis (IMF), also called agnogenic
thrombocytosis or primary (idiopathic) thrombocythaemia (of unknown origin) myeloid metaplasia, primary
is a clonal disorder characterised by markedly elevated myelofibrosis and myelosclerosis, is a clonal disorder
platelet count in the absence of any recognisable stimulus. characterised by proliferation of neoplastic stem cells at
Secondary or reactive thrombocytosis, on the other hand, occurs multiple sites outside the bone marrow (i.e. extramedullary
in response to known stimuli such as: chronic infection, haematopoiesis), especially in the liver and spleen, without
haemorrhage, postoperative state, chronic iron deficiency, an underlying etiology. Secondary myelofibrosis, on the other
malignancy, rheumatoid arthritis and postsplenectomy. hand, develops in association with certain well-defined
ET is an uncommon disorder and represents an marrow disorders, or it is the result of toxic action of chemical
overproduction of platelets from megakaryocyte colonies agents or irradiation.
without any added stimulus but no clonal marker is available The exact etiology is not known. Several chromosomal
to distinguish primary from secondary thrombocytosis. abnormalities have been reported but without a specific
Though an elevated platelet count is the dominant feature, cytogenetic abnormality. Fibrosis in the bone marrow is due
other cell lines may also be involved in the expansion of to overproduction of transforming growth factor-β,
neoplastic clone. osteosclerosis of the bone is related to osteonectin and marrow
The underlying pathophysiologic mechanism in ET is the angiogenesis is due to increased production of vascular
SECTION II
absence of control by thrombopoietin that regulates endothelial growth factor (VEGF).
endomitosis in the megakaryocytes to produce platelets. This Clinical Features
results in uncontrolled proliferation of not only mega-
karyocytes but also the platelets. There is probably role of The disease begins in the late middle life and is gradual in
heredity in ET since families with ET have been reported. onset. Both sexes are affected equally. The symptomatology
includes the following:
1. Anaemia with constitutional symptoms such as fatigue,
Clinical Features
weakness and anorexia.
The condition has an insidious onset and is more frequent in 2. Massive splenomegaly producing abdominal discomfort,
older people. Haemorrhagic and thrombotic events are pain and dyspnoea.
common. These include the following: 3. Hepatomegaly is present in half the cases.
1. Arterial or venous thrombosis. 4. Petechial and other bleeding problems are found in about
20% cases.
2. Easy bruisability following minor trauma. 5. Less common findings are lymphadenopathy, jaundice,
3. Spontaneous bleeding. ascites, bone pain and hyperuricaemia.
4. Transient ischaemic attack or frank stroke due to platelet
aggregation in microvasculature of the CNS. Laboratory Findings

1. Mild anaemia is usual except in cases where features of
Laboratory Findings
polycythaemia vera are coexistent.
The prominent laboratory features pertain to platelets. 2. Leucocytosis at the time of presentation but later there
These include the following: may be leucopenia.
Haematology and Lymphoreticular Tissues
1. Sustained elevation in platelet count (above 400,000 μl). 3. Thrombocytosis initially but advanced cases show
thrombocytopenia.
2. Blood film shows many large platelets, megakaryocyte
fragments and hypogranular forms. 4. Peripheral blood smear shows bizarre red cell shapes, tear
drop poikilocytes, basophilic stippling, nucleated red cells,
3. Consistently abnormal platelet functions, especially immature leucocytes (i.e. leucoerythroblastic reaction),
abnormality in platelet aggregation. basophilia and giant platelet forms.
4. Bone marrow examination reveals a large number of 5. Bone marrow aspiration is generally unsuccessful and
hyperdiploid megakaryocytes and variable amount of yields ‘dry tap’. Examination of trephine biopsy shows
increased fibrosis. focal areas of hypercellularity and increased reticulin
network and variable amount of collagen in which clusters
of megakaryocytes are seen well preserved.
Treatment and Complications
6. Extramedullary haematopoiesis can be documented by
ET runs a benign course and may not require any therapy. liver biopsy or splenic aspiration.
Treatment is given only if platelet count is higher than one
million. Complications of ET are occurrence of acquired von Treatment and Complications
Willebrand’s disease and bleeding but incidence of Chronic idiopathic myelofibrosis does not require any
thrombosis is not higher than matched controls. specific therapy. Anaemia and ineffective erythropoiesis